Esters of tertiary butyl acetic acid



Patented Sept. 1, 1936 UNETED TA PATENT OFFICE to Mallinckrodt ChemicalWorks, St. Louis, Mo., a corporation of Missouri No Drawing. ApplicationNovember 3, 1934, Serial No. 751,417

'1 Claims. (01. 260-106) This invention relates to derivatives oftertiary butyl acetic acid, and with regard to certain more specificfeatures, to ester derivatives corresponding to the type formula:

- (CH3)3C.CH2.COOR

wherein R is a hydrocarbon radical.

This application is in part a continuation in part of our application,Serial No. 666,512, filed April 17, 1933, and entitled Acyl halides oftertiary butyl acetic acid, now Patent No. 2,034,850,

dated March 24, 1936.

Among the several objects of the invention may be noted the provision ofa series of esters of tertiary butyl acetic acid corresponding to theabove '5 type formula which all embody the therapeutic effect of thepresence of the quarternary carbon atom. Other objects will be in partobvious and in part pointed out hereinafter.

The invention accordingly comprises the ele- 20 ments and combination ofelements, and features of composition, which will be exemplified in thesubstances hereinafter described, and the scope of the application ofwhich will be. indicated in the following claims.

25 It has recently been determined that certain organic productsincluding as a constituent.

thereof a quarternary carbon atom (that is, a carbon atom to which aredirectly linked four other'carbon atoms) have valuable therapeutic 30properties, particularly in the field of hypnotics, sedatives,soporifics, analgesics, and bactericides and the like.

Among the products so constituted, the esters of tertiary butyl aceticacid are a most valuable group. These esters have been determined tohave valuable hypnotic or'sedative or soporific effects .whenadministered therapeutically, such e'fiects being markedly improved oversimilar effects obtained from analogous compounds (such 40 as the estersof secondary butyl acetic acid) not containing the quarternary carbonatom. The enhanced efiect seems to be due to the fact that thequarternary carbon atom represents the maximum degree of branching inthe structure of the compound.

The esters of the present invention may be prepared, generally, in oneof the two following manners:

Method A The ester is prepared by direct esterification of tertiarybutyl acetic acid with the appropriate alcohol, according to the typereaction: (CH3) aCflllacoX-l-ROH-r- 55 (CH3) 3C.CH2.COOR+H2O.

R in the above reaction indicates an alcohol radical."

- Tertiary butyl acetic acid is obtained in pure form according to thecopending application of the present inventors and Walter R. Trent,Serial 5 No. 666,511, filed April 17, 1933, now Patent No. 2,004,066,dated June 4, 1935.

Method B I The ester is prepared by treatment of an acyl 1o halide (forexample, acyl chloride) of tertiary butyl acetic acid with theappropriate alcohol according to the' type reaction:

(CI-I3) 3C.CHz.COX+ROH- (CHa)sC.CHzCOOR+HX.

R in the above reaction indicates an alcohol radical, while X'indicatesa halogen atom.

Tertiary butyl acyl halides are obtained in pure form according to theaforesaid copending application of the present inventors, Serial No.666,512, filed April 17, 1933.

. EXAMPLE 1 Methyl ester .of tertiary butyl acetic acid Tertiary butylacetyl chloride was added slowly, in molecular proportions, to puremethanol. After warming for a short time on a steam bath, the productwas washed with water, and sodium bicarbonate solution, and then driedand fractionated. The yield was practically quantitative.

The ester, which was a colorless liquid, had a boiling point of 126.5 C.under 739 mm. pressure ;(Cottrell apparatus); an index of refraction at20 0., with respect to the sodium-D line, of 1.3981; and a density at 20C., compared with that of water at 4 C., of 0.8710. Its observedmolecular refraction value was 36.06 against an an equal calculatedvalue.

' EXAMPLE 2 40 Ethyl ester of tertiary butyl acetic acid mm. pressure;an index of refraction of 1.4010;

and a density of 0.8604. Its observed molecular refraction value was40.70 against a calculated value of 40.68.

EXAMPLE 3 n-Propyl ester of tertiary butyl acetic ocid This was preparedas in Example 1, using npropanol in place of the methanol.

The ester, which was likewise a colorless liquid, had a boiling point of92 C. under 65 mm. pressure; an index of refraction of 1.4067; and adensity of 0.8585. Its observed molecular refraction 5 value was 45.32,against a calculated value of E M M. Isopropyl ester of tertiary butylacetic acid This was prepared as in Example 1, using isopropanol inplace of the methanoL The ester, which was likewise acolorless liquid,

had a boiling point of 94 to.95:C. under.110 to 112 mm. pressure; anindex oi refraction of 1.4030; and a density of 0.8467.

Exsiyrrnrijjv I n-Butyl ester of tertiary butyl acetic acid This wasprepared as in Example 1, using nbutanol in place of the methanol.- I

The ester, which was likewise a colorless'liquid, had a boiling point of91 C. under 30 mm. pressure; an index of refraction of 1.4118; anddensity of 0.8568. Its observed molecular refraction value was 49.97,against a calculated value of EXAMPLE sec-Batyl ester of tertiary butylacetic acid This was prepared as in Example 1, using secbutanol in placeof the methanol. The ester, which was likewise a colorless liquid, had aboiling point of104" to 105 C. under 80 mm. pressure; an index ofrefraction of 1.4096 to 1.4100; and a density of 0.8510.

EXAMPLE 7 4,4-dimethyZpentanol-2 ester of tertiary butyl acetic acid 40This was prepared as in Example 1, using'4,4-

dimethyl-pentanol-2 in place of the methanol.

The ester, which was a colorless liquid, had a boiling point of 92 to 94C. under 7 to 8 mm. pressure; and an index of refraction of 1.4195.

This substance is of particular interest, as it contains a quarternarycarbon atom in the alcohol'radical as wellas in the acid radical.

I EXAMPLE 8 Allyl ester of tertiary butyl acetic acid This was preparedas in Example 1, using allyl alcohol in'place of the methanol. I I

The ester, which was likewise a colorless liquid,

had aboiling point of 104 to 105 C. under to 112 mm. pressure; an indexof refraction of 1.4200 ;,and a density of 0.8767,.

EXAMPLE 9 EXAMPLE 10 Bomyl ester of tertiary butyl acetic acid Menthylester of tertiary butyl acetic acid This was prepared as in Example 1,using menthol in place of the methanol. The yield,

" however, was only 72-76% of theoretical.

The ester, which was a colorless oil, had a boiling point of 114 to 115C. under 4 to 4.5 mm. pressure; and an index of refraction of 1.4500.

Numerous other esters can be prepared by analogous methods. I

In this specification the stated index of'refraction values are at 20 C.with respect to the sodium-D line. The density values are at 20 C. withrespect to water at 4 C. Pressure is stated in millimeters of mercury.

In view of the above, it will be seen that the several objects of theinvention have been achieved and other advantageous results attained.

As many changes could be made in carrying out the above syntheses and inefiecting the above compositions without departing from the scope of theinvention, it is intended that all matter contained in the abovedescription shall be interpreted as illustrative and not in a limitingsense.

We claim: 1. An ester of tertiary butyl acetic acid corresponding to thetype formula:

(CH3) 3C.CH2.COQR

where R. is an alkyl.

2. An ester of tertiary butyl acetic acid corresponding to the typeformula:

(CH3) aoonacoon where R is an alkyl containing a quarternary carbon atomin its structure.

3. An ester of tertiary butyl acetic acid corresponding to the typeformula:

(CH3) 3C.CH2.COOR

(CH3) 3C.CH2.COOR

where R is a substituent selected from a group consisting of alkyls,alkylenes, and aralkyls.

FRANK C. WHITMORE. AUGUST H. HOMZEYER;

Certificate of Correction Patent No. 2,052,995. September 1, 1936. FRANKC. W'HITMORE ET AL.

It is hereby certified that errors appear in the printed specificationof the above numbered patent requiring correction as follows: Page 1,second column, line 15, in the formula, insert a period before COOR;line 33, for 126.5 C. read 126.5 0.; page 2, second column, line 5, forvorneol read borneol; and that the said Letters Patent should be readwith these corrections therein that the same may conform to the recordof the case in the Patent Oflice.

Signed and sealed this 10th day of November, A. D. 1936.

[SEAL] HENRY VAN ARSDALE,

Acting Commissioner of Patents.

